The present invention relates generally to the area of the preparation of liquid samples in a sample vessel, particularly to the sampling fluid from a sample vessel or the filling of sample fluid into a sample vessel, wherein the sample vessel is sealed on the top side with a septum. The invention relates particularly to the preparation of samples to be analyzed using NMR spectroscopy. However, the applicability of the invention is not limited to this area.
NMR spectroscopy is a widely used method of measurement with which chemical compounds can be analyzed. In NMR spectroscopy, a sample to be measured, situated in a test tube, is typically placed into a probehead and measured in the NMR spectrometer.
A so-called XYZ liquid handler is typically used to prepare samples for NMR measurements. Such liquid handlers comprise a pipetting device that can be moved in three spatial directions (X, Y, Z). A plurality of samples to be studied are prepared in sample vessels, each of which is sealed with a septum. These septa must be pierced by a needle with a bevel in order to reach the sample. The XYZ liquid handler usually has a so-called septum piercing needle for this purpose. The septum piercing needle is typically used both for piercing the septum and for handling the sample fluid.
A liquid handler in which freely hanging septum piercing needles are used became known from the company brochure “SamplePro Tube—Customer Information” published by Bruker BioSpin GmbH, Silberstreifen 4, D-76287 Rheinstetten and dated 27 April 2015. This liquid handler further comprises a holding-down device for sample vessels.
This liquid handler enables simple monitoring of the sample position with the aid of the holding-down device through simultaneous measurement of a motor current during movement to a set Z-position (vertical position) for some but not all commonly used sample vessels. Particularly with densely arranged vessels with a small opening, it is not possible to check the sample position.
Besides sample vessels, which can sometimes have a relatively large top-side opening (3 to 5 mm diameter), objects with very small inside diameters (such as NMR tubes, for example), among other things, must also be filled. There are NMR tubes that must be filled with prepared sample fluid which have a 1.0 mm or 1.7 mm outside diameter and correspondingly small inside diameter of only 0.7 mm or 0.8 mm or 1.4 mm. Such NMR tubes can only be approached with a thin needle with small outside dimensions. However, needles with outside diameters of less than 1 mm are too labile to pierce septa, which are up to 3 mm thick.
Septum piercing needles can have a length of up to 200 mm with outside diameters between 0.5 mm and 1.5 mm. They are therefore relatively labile. It is then necessary to guide the needles in order to prevent buckling or bending of the needles.
In the “Triathlon user manual” cited at the outset, a pipetting device for a liquid handler is described that has a piercing needle and a sample needle. The piercing needle is used to pierce a septum sealing a sample vessel. The analysis needle is arranged concentrically within the piercing needle and is used to handle sample fluids.
Due to its construction and mechanism for moving the pipetting device, however, a liquid handler is prone to certain imprecisions in the spatial alignment of the pipetting device. Furthermore, the sample vessels used have (dimensional) tolerances. The positioning of the sample vessels in a holding device is also subject to certain (positional) imprecisions. This can result in deviations in the relative position between the pipetting device and the sample vessels, quite possibly on the order of +/−1 mm. Moreover, there are sample vessels with very narrow openings in NMR applications, such as so-called NMR SampleJet tubes, for example, which have an opening diameter of approximately 2 mm. The danger therefore exists of the needles used in the pipetting device of the liquid handler are not striking the center of the septum or even hitting an upper edge of the sample vessel. Such out-of-position of the needles must be avoided, since it would inevitably result in the destruction of the needles.
Furthermore, the friction of the septum retains a needle that is inserted into the septum. When the needle is pulled out, the septum, or a sample vessel comprising the septum, must therefore be actively pushed off. This can be accomplished by anchoring the sample vessel firmly on a work plate, although that requires an individualized and often elaborate mechanism for each position and vessel shape.